The compound 4-(2'-methoxyethyl)phenol, a substituted phenethanol ether prepared in accordance with the present invention, is a known compound. It is used as an intermediate in the production of 1-[4-(2-methoxyethyl)phenoxy]-3-[1-(1-methoxyethyl)amino]-2-propanol, a beta-adrenergic blocker known as metroprolol tartrate and described in 2 Pharmaceutical Manufacturing Encyclopedia, 1009-1010 (2nd ed. 1988.).
Several methods have been employed in the past to manufacture 4-(2'-methoxyethyl)phenol. A method is described in Baird et.al., Neighboring Carbon and Hydrogen. LI.sup.1 Dienones from Ar, .THETA.-3 Participation. Isolation and Behavior of Spiro (b 2,5; ocra-I,4-diene-3-one, 85 Am. Chem. Soc'y 567, 575 (1963) and in Communication to the Editor from Baird, et.al., 79 Am. Chem. Soc'y 756-757 (1957). In that method, 4-(2,-methoxyethyl)phenol is synthesized from phenylacetic acid through a multi-step process.
French Patent 2,487,338 discloses the preparation of 4-(2,-methoxyethyl)phenol utilizing brominated alkoxyphenol as a starting material. The method utilizes a multi-step process which includes a technically difficult Grignard reaction
Belgian patent 885,030 discloses another method for the preparation of 4-(2'-methoxyethyl)phenol. In that method, the starting material is 4-hydroxystyrene. Several steps are used to obtain the final product.
Still another method for the production of 4-(2'-methoxyethyl)phenol is disclosed in Hallberg, et.al., A New Route to 4-(2-Methoxyethyl)phenol via Palladium-catalyzed Arylation of Methyl Vinyl Ether, 15(13) Synthetic Com., 1131-6 (1985; wherein 4-(2'-methoxyethyl)phenol is prepared via palladium-catalyzed arylation of methyl vinyl ether. The palladium catalyzed reaction of methyl vinyl ether with 4-bromonitrobenzene, followed by hydrogenation and subsequent diazotization forms 4-(2'-methoxyethyl)phenol.
One of the disadvantages of the above referenced processes is that they include several, often complex, steps which give rise to economical and ecological problems. Furthermore, another disadvantage of some of the above referenced processes was that they utilize expensive starting material.
According to the present invention, a simple economical method is disclosed wherein 4-hydroxyphenylglyoxal dimethyl acetal is catalytically reduced to prepare 4-(2'-methoxyethyl)phenol. The method is also employed to prepare other substituted phenethanol ethers which are believed to be useful as intermediates in pharmaceutical products by the catalytic reduction of corresponding substituted phenylglyoxal acetals. Furthermore, according to the present invention, a simple economical process is described for the preparation of certain such acetals and, more particularly, 4-hydroxyphenylglyoxal dialkyl acetals from 4-hydroxyacetophenone. Co pending U.S. Pat. application Ser. No. 07/628,238, filed on Dec. 13, 1990, discloses the preparation of certain hydroxyaromatic ketoacetals from hydroxyaromatic methylketones. The entire content of that application is incorporated herein and is part hereof by reference.
German patent 2,432,563 discloses the oxidation of substituted acetophenones using alkyl nitrites in alcohol/hydrochloric acid to prepare substituted phenylglyoxalacetals. Furthermore, German Patent No. 3,539,629 discloses a method of oxidizing substituted acetophenones using dinitrogentrioxide in alcohol/hydrochloric acid to prepare appropriate substituted phenylglyoxal acetals.
These and other advantages and objects of the present invention will become apparent from the following description.